Wednesday, February 19, 2020

FDA Approves Nouress (cysteine hydrochloride) Injection for Treating Neonate Patients Requiring Total Parenteral Nutrition (TPN)

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Avadel Pharmaceuticals plc (Nasdaq: AVDL) announced that the U.S. Food and Drug Administration (FDA) has approved Nouress (AV001), a cysteine hydrochloride injection, a critical drug for treating neonatal patients requiring total parenteral nutrition (TPN).

In addition, Avadel announced today that the United States Patent and Trademark Office (USPTO) recently issued United States Patent No. 10,493,051 covering cysteine solutions, including the approved Nouress product. This patent is listed in the Orange Book for Nouress and is set to expire in March of 2039. Avadel has additional U.S. patent applications pending for Nouress.
“We are pleased to receive FDA approval for Nouress, which validates our strategy of developing innovative medicines for patients,” said Greg Divis, Chief Executive Officer of Avadel. “Nouress is the fourth FDA approved product in our sterile injectable hospital business. The cash flow generated by this legacy business is supporting the clinical development costs from our lead program, FT218, which is currently expected to announce topline data from the pivotal Phase 3 REST-ON trial in the second quarter of 2020. We believe that as a once-nightly formulated sodium oxybate, FT218, if approved by the FDA, has the potential to take a significant share of the twice-nightly sodium oxybate market, which is currently valued at an estimated annualized rate of $1.7 billion.”
Avadel is currently evaluating the timing and process for a commercial launch of Nouress in the United States. In this regard, a competitor received FDA approval earlier this year for its cysteine hydrochloride injection and more recently was granted a U.S. patent, which Avadel is assessing along with other market factors. 
Due to a historical lack of reliable supply, U.S. markets previously imported cysteine hydrochloride injection from Canada under special FDA rules allowing shortage drugs to be sourced abroad if no domestic supplies are available. With FDA approvals of Nouress and another U.S. company’s cysteine hydrochloride injection earlier this year, Avadel expects the domestic supply of cysteine hydrochloride injection will be sufficient to support the entire U.S. market, which, under FDA regulations, should preclude further import or U.S. marketing of unapproved cysteine hydrochloride injection products.  Under these potential market conditions, the U.S. annual market for cysteine hydrochloride could be greater than $50 million.

Tuesday, February 18, 2020

FDA Approves Conjupri (levamlodipine maleate) for the Treatment of Hypertension

 The board of directors (the “Board”) of CSPC Pharmaceutical Group Limited (the “Company”, together with its subsidiaries, the “Group”) is pleased to announce that Conjupri® (levoamlodipine maleate) tablets has received marketing approval from the U.S. Food and Drug Administration (FDA) for the treatment of hypertension. Based on our knowledge, this is the first New Drug Application (NDA) ever submitted to the FDA by Chinese pharmaceutical companies, and now granted full approval following a standard review by the FDA.


Levoamlodipine is the purified (S)-amlodipine, the pharmacologically active enantiomer in amlodipine (a racemic mixture of (R)- and (S)-amlodipine), for the treatment of hypertension. Amlodipine is a third-generation calcium channel blocker first developed and marketed by Pfizer as NORVASC® (amlodipine besylate) tablets in 2.5 mg, 5.0 mg, and 10.0 mg in 1992. The approved Conjupri® (levoamlodipine maleate) tablets come in 1.25 mg, 2.5 mg and 5.0 mg.
Levoamlodipine maleate tablets have been marketed by the Group as Xuanning ( 玄寧) in China since 2003. The clinical development of levoamlodipine maleate tablets in the U.S. was based on the safety and efficacy data demonstrated in China and data showing that levoamlodipine has less adverse events than amlodipine.
This NDA approval allows the Group to market Conjupri® in the U.S. and also paves the way for marketing in other parts of the world. As the first levoamlodipine approved by the FDA, Conjupri® is qualified to be the reference standard for drugs with the same active ingredient.

The NDA approval of levoamlodipine maleate tablets in the U.S. is a manifestation of the Group’s commitment to innovation and to bringing the best medicines to patients worldwide.

Monday, February 17, 2020

FDA Approves Dayvigo (lemborexant) for the Treatment of Insomnia in Adult Patients


In continuation of my update on lemborexant

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) today announced that the U.S. Food and Drug Administration (FDA) approved the new drug application for its in-house discovered and developed orexin receptor antagonist Dayvigo (lemborexant). Dayvigo was approved for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults1. In the United States, Dayvigo will be commercially available in 5 mg and 10 mg tablets following scheduling by the U.S. Drug Enforcement Administration (DEA), which is expected to occur within 90 days.

The mechanism of action of lemborexant in the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to orexin receptors OX1R and OX2R is thought to suppress wake drive. Lemborexant binds to orexin receptors OX1R and OX2R and acts as a competitive antagonist with stronger inhibition effect to OX2R*.
The approval was based on the results of a clinical development program that included two pivotal Phase III studies (SUNRISE 2 and SUNRISE 1), which evaluated Dayvigo versus comparators for up to one month and Dayvigo versus placebo for six-months, respectively, in a total of about 2,000 adult patients with insomnia. From these studies results, Dayvigo demonstrated statistically significant superiorities on sleep onset and sleep maintenance compared to placebo in both subjective and objective evaluations.
Across SUNRISE 2 and SUNRISE 1, Dayvigo was not associated with rebound insomnia following treatment discontinuation, and there was no evidence of withdrawal effects following Dayvigo discontinuation at either dose. In addition, the development program included multiple safety studies evaluating effects on postural stability, cognition, driving performance and respiratory safety.
  • SUNRISE 2 was a long-term (six month), randomized, double-blind, placebo-controlled, multi-center, trial in adult patients age 18 or older who met DSM-5** criteria for insomnia disorder. Patients were randomized to placebo (n=325), Dayvigo 5 mg (n=323), or Dayvigo 10 mg (n=323) once nightly. The primary efficacy endpoint was the mean change from baseline to end of treatment at six months for patient-reported (subjective) sleep onset latency (sSOL), defined as the estimated minutes from the time that the subject attempted to sleep until falling asleep. Pre-specified secondary efficacy endpoints were change from baseline to end of treatment at six months for patient reported sleep efficiency (sSE; defined as the proportion of time spent asleep during time in bed) and subjective sleep onset and sleep maintenance (sWASO; defined as the minutes of wake from the onset of persistent sleep until lights on). The primary and pre-specified secondary efficacy endpoints were measured using a Sleep Diary. In SUNRISE 2, Dayvigo 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, sSOL, compared to placebo. Dayvigo 5 mg and 10 mg also showed statistically significant superiority in sSE and sWASO.1
  • SUNRISE 1 was a short-term (one month), randomized, double-blind, placebo- and active-controlled, multi-center, parallel-group clinical trial in adult female subjects age 55 and older and male subjects 65 years and older who met DSM-5 criteria for insomnia disorder. Patients were randomized to placebo (n=208), Dayvigo 5 mg (n=266) or 10 mg (n=269) or active comparator (n=263) once nightly. The primary efficacy endpoint was the mean change in latency to persistent sleep (LPS; defined as the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness) from baseline to end of treatment (day 29/30), as measured by overnight polysomnography (PSG) monitoring. The pre-specified secondary efficacy endpoints in SUNRISE 1 were the mean change from baseline to end of treatment (day 29/30) in sleep efficiency (SE) and wake after sleep onset (WASO) measured by PSG. In SUNRISE 1, Dayvigo 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, LPS, compared to placebo. Dayvigo 5 mg and 10 mg demonstrated statistically significant improvement in SE and WASO compared to placebo.1
    The most common adverse reaction (reported in 5% or more of patients treated with Dayvigo and at least twice the rate of placebo) in SUNRISE 2 (the first 30 days) and SUNRISE 1 was somnolence (Dayvigo 10 mg, 10%; Dayvigo 5 mg, 7%; placebo, 1%).

Friday, February 14, 2020

Experimental antiviral prevents MERS-CoV in rhesus macaques

In continuation of my update on remdesivir 
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The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.
The new report from NIH's National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.
MERS-CoV is closely related to the 2019 novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.
Remdesivir has previously protected animals against a variety of viruses in lab experiments. The drug has been shown experimentally to effectively treat monkeys infected with Ebola and Nipah viruses. Remdesivir also has been investigated as a treatment for Ebola virus disease in people.
The current study was conducted at NIAID's Rocky Mountain Laboratories in Hamilton, Montana. The work involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV; those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.
The scientists observed the animals for six days. All control animals showed signs of respiratory disease. Animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage. Animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.
The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and COVID-19, the disease that SARS-CoV-2 causes. Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.
The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also provided support for this study. Gilead Sciences, Inc., developed remdesivir, also known as GS-5734, and collaborated in the research.
MERS-CoV emerged in Saudi Arabia in 2012. Through December 2019, the World Health Organization had confirmed 2,499 MERS-CoV cases and 861 deaths (or about 1 in 3). Because about one-third of MERS-CoV cases spread from infected people being treated in healthcare settings, the scientists suggest that remdesivir could effectively prevent disease in other patients, contacts of patients, and healthcare workers. They also note the drug might help patients who are diagnosed with MERS or COVID-19 if given soon after symptoms start.

FDA Approves Caplyta (lumateperone) for the Treatment of Schizophrenia in Adults

Intra-Cellular Therapies, Inc. (Nasdaq:ITCI), a biopharmaceutical company focused on the development of therapeutics for central nervous system (CNS) disorders, today announced that Caplyta (lumateperone) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia in adults. The Company expects to initiate the commercial launch of Caplyta in late Q1 2020.


The efficacy of Caplyta 42 mg was demonstrated in two placebo-controlled trials, showing a statistically significant separation from placebo on the primary endpoint, the Positive and Negative Syndrome Scale (PANSS) total score. The most common adverse reactions (≥5% and twice the rate of placebo) for the recommended dose of Caplyta vs placebo were somnolence/sedation (24% vs.10%) and dry mouth (6% vs. 2%).
In pooled data from short term studies, mean changes from baseline in weight gain, fasting glucose, triglycerides and total cholesterol were similar between Caplyta and placebo. The incidence of extrapyramidal symptoms was 6.7% for Caplyta and 6.3% for placebo.
“We believe Caplyta provides healthcare providers a new, safe and effective treatment option to help the millions of adult patients with schizophrenia,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. “This approval represents the culmination of years of scientific research. We are especially grateful to the patients, their caregivers, and the healthcare professionals who have contributed to the development of Caplyta.”
Schizophrenia is a serious mental illness impacting approximately 2.4 million adults in the United States. The clinical presentation of schizophrenia is diverse. Acute episodes are characterized by psychotic symptoms, including hallucinations and delusions, often requiring hospitalization. The disease is chronic and lifelong, often accompanied by depression and gradual deterioration of social functioning and cognitive ability. Patients with schizophrenia often discontinue treatment as a result of side effects such as weight gain and movement disorders.
“Schizophrenia is a complex disease that severely impacts patients and their families,” said Jeffrey A. Lieberman, M.D., Lawrence C. Kolb Professor and Chairman of Psychiatry, Columbia University, College of Physicians and Surgeons and Director, New York State Psychiatric Institute. “Effective treatment provided in a timely fashion can be game-changing for people living with schizophrenia. The efficacy and safety profile of Caplyta approved by the FDA, offers healthcare providers an important new option for treating people living with schizophrenia.”

Thursday, February 13, 2020

FDA Approves Ubrelvy (ubrogepant) for the Acute Treatment of Migraine

In continuation of my update on Ubrelvy (ubrogepant)


Allergan plc (NYSE: AGN),  announced that the U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for Ubrelvy (ubrogepant) for the acute treatment of migraine with or without aura in adults. Ubrelvy™ is the first and only orally-administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the treatment of migraine attacks once they start. Migraine is a neurological disease characterized by intermittent migraine attacks with symptoms that are often incapacitating. Migraine afflicts 31 million Americans and is the third most common disease and second leading cause of disability worldwide.

"The FDA's approval of Ubrelvy™, a new oral option that is effective in the acute treatment of migraine attacks, is a much-welcomed development for me and for many who care for patients. I can offer my migraine patients a new treatment option that may work for them," said Dr. Peter Goadsby, Neurologist and Professor at King's College, London, and University of California, San Francisco, and a paid consultant for Allergan. "Perhaps even better, I am able to offer a new sense of hope for my patients who struggle for relief from this highly disabling problem."
In clinical trials supporting the FDA's approval, Ubrelvy™ provided quick pain relief for the majority of migraine patients. Ubrelvy™ also met co-primary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, hypersensitivity to light, or hypersensitivity to sound), a recent, more stringent standard of efficacy the FDA set in 2018. Ubrelvy™ provided lasting relief up to 24 hours as well. Ubrelvy™ works in a new way by blocking CGRP, a protein that is released during a migraine attack, from binding to its receptors. It works without constricting blood vessels, which some older treatments are known to do. Ubrelvy™ is non-narcotic, not scheduled, and does not have addiction potential. It has been approved with two dose strengths, 50 mg and 100 mg, and is specially designed so healthcare providers can provide a personalized treatment approach for appropriate patients.
"As someone living with migraine for 14 years, my life seems to be on pause when I experience a migraine attack," said Kristin Molacek, Ubrelvy™ clinical trial patient. "During the clinical trial, my experience with Ubrelvy™ was positive. It relieved the migraine symptoms that bothered me the most without serious side effects. We have needed this type of on-demand oral relief for a very long time, and I look forward to having the ability to better manage my migraine attacks."
"We are extremely pleased that Ubrelvy™ is now approved by the FDA. As the first oral gepant, Ubrelvy™ offers a new and different type of acute treatment option for people living with the debilitating pain and other symptoms of migraine," said David Nicholson, EVP and Chief R&D Officer, Allergan. "Its oral administration with two dose strengths allows for treatment flexibility and relief when a migraine attack occurs. As we continue to drive innovation in migraine treatment, we are very proud to offer patients another option, and we are confident that it will make a difference for those in need. At Allergan, we believe that migraine patients deserve access to all new medications for this debilitating disease."
About Ubrelvy (ubrogepant)
Ubrelvy (ubrogepant) is a novel, highly potent, orally-administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the acute treatment of migraine with or without aura in adults that is an option for a wide range of patients who experience migraine attacks. It works in a new way by blocking CGRP, a protein released during a migraine attack, from binding to its receptors. It works without constricting blood vessels, which some older treatments are known to do. CGRP receptor antagonism is a completely new mechanism of action for the acute treatment of migraine.
The FDA approval for Ubrelvy is based on four clinical studies (ACHIEVE I, ACHIEVE II, UBR-MD-04 and 3110-105-002), which demonstrated efficacy, safety and tolerability of orally-administered Ubrelvy in the acute treatment of migraine. The two pivotal Phase 3 clinical trials (ACHIEVE I and ACHIEVE II) established the safety and efficacy profile of Ubrelvy. Both 50 mg and 100 mg dose strengths demonstrated significantly greater rates of pain freedom and freedom from the most bothersome migraine-associated symptom at two hours, compared with placebo.
Nausea was the most common adverse event reported in 1.7-4.1% of patients at various doses during the pivotal studies, compared to 1.6-2.0% of patients who received placebo. There were no serious adverse events within 48 hours of a dose. Additionally, the safety study (UBR-MD-04) reinforced the long-term safety and tolerability of Ubrelvy for both the 50 mg and 100 mg dose strengths. Our research shows that Ubrelvy was well tolerated with an adverse event profile similar to placebo.

Wednesday, February 12, 2020

Overdose, Relapse After Buprenorphine Discontinuation High

In continuation of my update on buprenorphine


Buprenorphine treatment may be needed for several years after an opioid overdose to reduce the risk of overdose and other adverse events, according to a study published online Dec. 2 in The American Journal of Psychiatry.
Arthur Robin Williams, M.D., from the New York State Psychiatric Institute at the Columbia University Medical Center in New York City, and colleagues used the MarketScan multistate Medicaid claims database (2013 to 2017) to identify adults (18 to 64 years of age) who received buprenorphine continuously for ≥180 days. Outcomes were assessed by buprenorphine duration period (six to nine months, nine to 12 months, 12 to 15 months, and 15 to 18 months).
The researchers found that adverse events were common across all cohorts, and almost half of patients (42.1 to 49.9 percent) were seen in the emergency department at least once. Patients retained for 15 to 18 months (931 patients) had significantly lower odds of emergency department visits (odds ratio, 0.75), inpatient hospitalizations (odds ratio, 0.79), and filling opioid prescriptions (odds ratio, 0.67) in the six months following discontinuation, compared to patients retained on buprenorphine for six to nine months (4,126 patients). Across cohorts, approximately 5 percent of patients experienced one or more medically treated overdoses.
"Patients and families need guidance, social support, and better coordination of care to help facilitate long-term maintenance with buprenorphine for opioid use disorder," Williams said in a statement.

Tuesday, February 11, 2020

Exeltis USA, Inc. Announces the Approval of Slynd (drospirenone), the First and Only Progestin-Only Pill Providing Pregnancy Prevention with a 24/4 Dosing Regimen and 24-hour Missed Pill Window


Exeltis USA, Inc. a division of the global pharmaceutical group Insud Pharma, announced today that the US Food and Drug Administration (FDA) has approved the new drug application (NDA) for Slynd (pronounced "slind") containing drospirenone 4 mg, an oral contraceptive tablet for pregnancy prevention.
Slynd, a progestin (see above structure) -only pill (POP) is a novel estrogen-free oral contraceptive that is intended as a 24 active with 4 inactive tablet dosing regimen and also allows a 24-hour missed pill window.  This not only can mean favorable safety and efficacy but an improved bleeding profile and contraceptive efficacy for up to 24 hours in the event of a delayed or missed dose.
In clinical trials, Slynd (a synthetic form of progesterone that has a similar pharmacological profile to the natural hormone progesterone) showed no instances of thromboembolic events experienced by some women taking COCs, which by definition contain estrogen.  In addition, the safety of Slynd™ is supported by its approval with no black box warning unlike other combined oral contraceptives.  But for females with conditions that predispose to hyperkalemia (e.g. renal impairment, hepatic impairment and adrenal insufficiency), Slynd™ is contraindicated due to its anti-mineralocorticoid activity.
"This safety profile was demonstrated for all patients, including higher-risk populations like smokers, older women, and subjects with a Body Mass Index (BMI) >30," said Enrico Colli, MD, Chief Scientific Officer.
Salustiano Perez, President of Exeltis USA, Inc. observed "Slynd may be an excellent choice for women who need or want safe and effective oral contraception without the risks of estrogen. Slynd may be an ideal choice for a breastfeeding mother."
Slynd™ is indicated to prevent pregnancy among females of reproductive potential. Contraindications include renal impairment, adrenal insufficiency, presence or history of progestin sensitive cancers, liver tumors, benign or malignant, or hepatic impairment, or undiagnosed abnormal uterine bleeding.

Friday, February 7, 2020

New Antibiotic Xenleta Approved for Community-Acquired Bacterial Pneumonia

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Xenleta (lefamulin) has been approved to treat adults with community-acquired bacterial pneumonia, the U.S. Food and Drug Administration announced today.
Dosing of Xenleta is either an oral administration of 600 mg every 12 hours or an intravenous administration of 150 mg every 12 hours for five to seven days. Patients can be started on either intravenous or oral therapy or can transition from intravenous to oral therapy to accelerate hospital discharge.
Approval was based on data from two clinical trials of 1,289 patients with community-acquired bacterial pneumonia comparing Xenleta taken orally or intravenously to treatment with moxifloxacin with or without linezolid. Clinical success rates of patients treated with Xenleta were similar to those of patients treated with moxifloxacin with or without linezolid.
The most commonly reported adverse reactions with Xenleta include diarrhea, nausea, injection site reactions, elevated liver enzymes, and vomiting. The FDA notes that Xenleta can cause a prolonged QT interval, so patients with arrythmias, those taking antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval should avoid Xenleta. Patients with known hypersensitivity to lefamulin, other members of the pleuromutilin antibiotic class, or any components of Xenleta are also contraindicated. Health care providers should advise pregnant women and those who could become pregnant of the risk for fetal harm with Xenleta as shown in animal studies. Women who could become pregnant should use effective contraception during and two days after taking Xenleta.
Approval of Xenleta was granted to Nabriva Therapeutics. The drug is expected to be available in mid-September with a wholesale acquisition price of $205 per IV patient treatment day and $275 per oral patient treatment day.

Thursday, February 6, 2020

Nourianz Approved to Treat 'Off' Episodes in Parkinson Disease

In continuation of my update on Levodopa 
Nourianz (istradefylline) tablets have been approved as an add-on treatment to levodopa/carbidopa for adults with Parkinson disease experiencing "off" episodes, the U.S. Food and Drug Administration announced yesterday.
The drug is available in 20-mg or 40-mg doses, but the maximum recommended dosage in patients taking CYP3A4 inhibitors and those with moderate hepatic impairment is 20 mg once daily. The safety information for Nourianz states that use of the drug should be avoided in these patient populations.
Data from four 12-week placebo-controlled clinical studies demonstrated the effectiveness of Nourianz, a selective adenosine A2A receptor antagonist, in treating "off" episodes in 1,143 PD patients who were receiving treatment with levodopa/carbidopa. Compared with patients who received placebo, patients who received Nourianz experienced a statistically significant decrease in daily "off" time from baseline.
The most commonly reported adverse reactions with Nourianz included dyskinesia, dizziness, constipation, nausea, hallucination, and insomnia. The FDA noted that physicians should monitor patients for the development or progression of dyskinesia while taking Nourianz. A reduction in dosage or stoppage of Nourianz should be considered in the case of hallucinations, psychotic behavior, or impulsive/compulsive behavior. Nourianz should not be used during pregnancy, and women with childbearing potential should use contraception during treatment.